Anti-HIV agent - etravirine

Another class of drug in the antiretroviral cocktail used to keep HIV's effect at bay is the reverse transcriptase inhibitor.

There are numerous non-nucleoside reverse transcriptase inhibitors (NNRTIs) available, but, like the protease inhibitors, the virus mutates to develop resistance to them, so ever more new ones need to be developed that attack the virus by mechanisms to which it is still susceptible. As a result, J&J subsidiary Tibotec is also developing a new NNRTI, etravirine;¹ the need for new antiretroviral drugs is evidenced by the fact that the molecule entered clinical trials within a year of first being identified.

A double blind, randomised, placebo-controlled trial was carried out in 18 patients infected with HIV who had not previously been given antiretroviral drugs.2 Two-thirds of the subjects were given 900mg etravirine as monotherapy twice a day, the remainder placebo, for seven days. Plasma viral load fell significantly in those given the active, and only minor side-effects were seen, including somnolence.

It has also been investigated in patients who had previously been treated with antiretroviral drugs.³ It was given to a group of HIV patients who were failing NNRTI therapy with either efavirenz or nevirapine and with confirmed resistance to efavirenz. In an open label Phase IIa trial, 16 patients were given etravirine in place of the normal NNRTI component of their drug cocktail for seven days. A median decrease in viral load of 0.9 log10 copies/ml was seen, which carried on falling after treatment on day eight.

An open Phase II trial of etravirine as a long-term treatment has also taken place.⁴ Patients were given 800mg etravirine twice a day in addition to three or four other drug components, and after 48 weeks the viral load of all bar two patients had dropped below 50 copies/ml. Trials are continuing.